Virtual transmitter for bioreactor automation system

ABSTRACT

A bioreactor monitoring and/or control system utilizing only non-dedicated user input and information display devices, a digital controller and software, said system comprising:
     i) at least one diagnostic probe for measuring operating conditions in a bioreactor;   ii) signal conditioning and communication electronics which supply operating current and/or voltage to said probe and which convert the diagnostic signal into a format accessible by   iii) a digital controller which directly receives the format converted signal and transmits it to   iv) software which enables the display device to show the converted signal, and also to instruct the controller to implement changes in the operating conditions in the reactor, and   v) a software-based virtual transmitter which substantially replicates the keyboard, display, menu-tree and response of a physical sensor transmitter.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a division of U.S. patent application Ser. No.12/151,254, filed May 5, 2008, and titled “Virtual transmitter forbioreactor automation system,” which is incorporated by reference hereinin its entirety and for all purposes.

FIELD OF THE INVENTION

This invention relates to a novel design for visualizing segments of abioreactor monitoring and control system that is implemented insoftware, rather than hardware (i.e., a “virtual” system. A preferredapplication of this virtual system is in the control of a bioprocess,such as cell culture or fermentation.

BACKGROUND OF THE INVENTION

The production of biotech drugs, pharmaceuticals, neutraceuticals,bio-diesel fuel, as well as many foods and beverages utilizes live cellcultures to implement a biochemical growth process. Optimization of thisprocess during manufacturing requires the ability to control theenvironment in the bioreactor by detecting a multitude of processvariables and controlling their values to be within a specified range oftolerances. Real-time monitoring of these variables and calculationsbased on these values are performed in order to determine the efficacyof the bioprocess underway.

Recently, systems for controlling process variables applicable to abioprocess have become increasingly sophisticated. These systemsfrequently employ digital systems such as programmable logic chips(PLCs), micro-processor based software control systems, or a hybridarrangement. Advancements in processors, communication hardware,protocols and archival software systems have transformed the concept ofdata management during bio-processing from a luxury to a necessity. Theadvent of sophisticated digital systems has given the bio-processengineer the capability to repeatedly apply the same complex series ofactions to any bio-process. This has enabled large moleculepharmaceutical manufacturing to move towards the level ofreproducibility that semiconductor processing now enjoys. Additionally,the use of digital systems to implement supervisory control and dataacquisition (SCADA) now allows a smoother path to satisfying therequirements of good manufacturing process (GMP) doctrines as well as USFood and Drug Administration (USFDA) requirements. However, ascapabilities have expanded so have the costs; yet for fully automatedcontrol systems and data histories to become commonplace in the biotechindustry these process control systems need to be affordable andaccessible to even the smallest biotech manufacturing organizations. Oneroute to containing costs is to minimize functional redundancy in theautomated process monitoring and control systems.

Irrespective of the complexity of the automation system, each of thesecontrol and monitoring platforms for a bioreactor share some degree ofcommonality. The common elements include a human-machine interface(HMI), a controller, internal and network communications interfaces,instruments by which to measure data from sensors within the bioreactoror adjoining process equipment, and actuators by which to physicallyinterface to process equipment such as agitators, valves, pumps, massflow controllers (MFCs) and/or rotameters.

A prior art system is shown schematically in FIG. 1:

-   -   1.1 is the HMI,    -   1.2 is a unit that contains the controller and network        communications interfaces,    -   1.3 is a utility tower unit that contains sensor transmitters,        relays, and analog outputs for actuator control, as well as        electronics that aggregate and condition communications from        both transmitters and actuators,    -   1.4 is a materials handling unit for gases and/or liquids that        contains pumps and MFCs,    -   1.5 is a first bioreactor and,    -   1.6 is a second bioreactor also coupled to utility tower 1.3

Optionally, additional utility towers, pumps and bioreactors (3 and 4)can be operably connected to the same controller and HMI as shown. Notethat this architecture can be implemented using either an aggregateddesign where all of the components of bioreactor units 1 through 4 arepackaged in a single enclosure that can control multiple bioreactors(e.g., FIG. 2a , shows an Applikon i-Control unit (www.applikon.com) forcontrol of two bioreactors, where 2.1 is the HMI, 2.2 is a set ofintegrated pumps, and 2.3 shows two banks of rotameters and FIG. 2bshows several i-Control units in a network).

Alternatively, amodular design with multiple enclosures is possiblee.g., as shown in FIGS. 3a and 3b , which illustrates a Finesse TruViuRDPD automation system (www.finesse.com) where 3.1 is the HMI, 3.2 isthe utility tower, 3.3 is the pump tower, and 3.4 is the MFC unit). Theoptimal design employed by the end user is influenced by cost, space,maintenance, and ease-of-use requirements for each particularbio-process application. In general, a modular approach offers thegreatest flexibility to the end user.

A personal computer (PC) is often used as a terminal or interfacethrough which to access the automation controller and software. The HMIcan be a monitor and keyboard that are directly attached to the PC or aseparate touch screen display connected using a wireless device. If thePC is used as a terminal, the software values and instructions canreside there, and any executable code is downloaded to the controllerwhere it runs independently of the PC. In cost sensitive applicationssuch as research facilities, where process down-time is less of anissue, the controller can be directly implemented in the PC, whereas inapplications requiring high up-time, the controller is often implementedas a separate device to enhance the reliability of the system. Theseparate controller either has available, or alternatively is packagedwith, communications ports for communication with an external network inorder to send and receive user commands, instructions, and/or newexecutable code.

FIG. 4 shows a schematic of a typical utility tower implementation. Theutility tower is an enclosure housing the transmitters for thesensors/probes used in a bioprocess. Possible sensors include thosewhich measure:

-   -   1. pH,    -   2. Dissolved oxygen,    -   3. Pressure,    -   4. Temperature,    -   5. Foam level,    -   6. Liquid level,    -   7. Weight,    -   8. Agitator motor speed and/or rocking period and angle,    -   9. Pump motor speed or number of revolutions, and    -   10. Gas flow rate

In general all of these sensors will not utilize the same communicationprotocol. Some sensors output their signal as a 4 mA to 20 mA analogcurrent, others use HART (www.hartcomm.com), while still others useModBus, (trade mark of Gould Inc.) ProfiBus, FieldBus, DeviceNet (trademark of Device Net Vendor Assoc.), Ethernet, wired serial protocols suchas RS-232 or RS-485 or wireless such as Bluetooth (trade mark ofBluetooth SIG. Inc.) or 802.15 or WiFi 802.11g. Some sensors useproprietary communication protocols developed by their manufacturer. Inorder to efficiently send signals to the controller, all or at leastmost of these sensor signals must be transformed into a common protocoland then aggregated in the utility tower. The aggregated communicationline often employs serial communications using a bus. There are manydigital bus communication protocols including, but not limited to,ModBus, ProfiBus, DeviceNet, and FieldBus.

FIG. 4 shows a typical prior art utility tower in which 4.1 is a pHtransmitter, 4.2 is a dissolved oxygen transmitter, and 4.3 is thecommunication between these transmitters and their associated sensors,respectively, and 4.4 is the communication between these transmittersand the signal translator. These transmitters often use a HART protocoland therefore need to be sent through a device 4.5 that will translatethe HART signals into a suitable Bus protocol, such as ModBus. Thesignals are then sent to a main signal aggregator 4.6. Many of the otheranalog or digital signals come in on lines 4.7 from the bioreactor. Thepump and/MFC towers and are conditioned (translated) and aggregated in aseparate component 4.8. These signals are then sent on their own line4.9 to the main signal aggregator 4.6. The totality of the aggregatedsignals 4.10 is sent to the control tower, to be received by the serialinput device. Note that several aggregators and translators can besequenced, in order to expand the capacity and capability of the overallutility tower system.

Current practice calls for the sensor to connect to the bio-processSCADA system via a transmitter. A typical dissolved oxygen or pHtransmitter is shown schematically in FIG. 5 where 5.1 is thetransmitter enclosure, 5.2 is the display, 5.3 is the data entry keypad,5.4 is the cable to the sensor/probe, 5.5 is the sensor/probe, and 5.6is a data line output from the transmitter that carries the processvariable information (and in some cases, additional diagnosticinformation and/or secondary/tertiary process variables). This data linecan be a 4-20 mA analog or HART signal that is physically carried on 2wires and carries information about the oxygen concentration or pHmeasured by the probe/transmitter pair. The output signal can also beencoded using a variety of digital protocols (e.g., RS-232, RS-485 etc.)with the value of the process variable contained therein. A transmitteris typically mounted inside a utility (or transmitter) tower, where itsoutput signal is usually aggregated with that of other transmittersand/or actuators, and is sent to the control unit by the signal pathwaydescribed previously and illustrated in FIG. 4.

In this scenario, the power (e.g., 24 V DC) to the transmitter isprovided by the utility tower, the power to the sensor is provided bythe transmitter, and the signal from the sensor is received andconditioned by the transmitter. For transmitters having digitalcommunications capability, i.e., more than just a 4 to 20 mA outputsignal, the transmitter is subservient to the automation system; namely,the user inputs a command through the automation system's HMI and thesensor transmitter reacts accordingly.

For instance, a typical polarographic dissolved oxygen transmitter orelectrochemical pH sensor transmitter will allow the probe to becalibrated and then provide the calibrated probe signal as an output. Inthis scenario, the transmitter performs these tasks in response tocommands sent by the bioprocess automation system. Additionally, asshown in FIG. 4 or FIG. 5, a transmitter with a microprocessor cantransmit both the conditioned signal as well as raw signals from theprobe. Specifically, digital transmitters are capable of transmitting tothe bio-process automation system, both the signals with storedcalibrations applied to them, as well as the raw signals (voltage orcurrent or impedance) coming to the transmitters directly from theprobes. The raw signals from the probe are important as they can be usedin a diagnostic or trouble-shooting capacity. For instance, with a pHprobe, the raw output signal is the voltage (mV) developed in accordwith the Nernst equation. This raw voltage, when monitored over time,can give insight into the probe's performance (e.g., output range,drift, etc.); additionally the impedance of the probe is indicative ofits health (e.g., if the impedance rapidly drops to zero, a probefailure has occurred, and probe output should no longer be trusted as anaccurate measurement of pH).

Similar output and diagnostic signals are available from multiplesensors. It should be noted that although these signals are sometimesaccessible on the transmitter's display, they are often difficult orimpossible to access in a typical bio-process automation system.Similarly, in many inexpensive bio-process automation systems, only theprimary process variable from a sensor is measured and converted into adigitized form by proprietary electronics, so that the diagnosticinformation from raw signal values and/or secondary sensor signals arelost.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a typical prior art architecture for a bioprocess controlsystem where the bioreactors and associated liquid/gas handling systemare connected to a utility tower, which is controlled by a controller.In this Figure the controller is configured using a HMI.

FIG. 2a shows a utility tower having integrated liquid/gas handling andHMI. This unit is capable of controlling two bioreactors. FIG. 2b showsa typical network architecture, where multiple utility towers areconnected to a SCADA system using OPC and the Ethernet.

FIGS. 3a and 3b show a modular utility tower system where the liquid/gashandling and HMI are packaged separately. The utility tower now containsonly sensor transmitters and signal translators and aggregators.

FIG. 4 is a schematic which shows the layout of a prior art utilitytower containing transmitters, a translator for the transmitters toconvert their output to a digital protocol, and signal aggregators.

FIG. 5 is a schematic which shows a prior art transmitter connected to asensor via a cable.

FIG. 6 shows an automation system HMI. The display provides an overviewof the process, including the bioreactor configuration, associatedhardware, control parameters and their corresponding set points.

FIG. 7a shows a configuration page from an automation system HMI. Thecontrol parameters are enumerated and configuration windows can be usedto set the control strategy.

FIG. 7b shows a typical sensor page from an automation system HMI. Thesensor has an associated parameter faceplate, a command faceplate withtabs indicating the different functions, and separate windows displayinginformation about the sensor.

FIG. 8 shows the schematic layout of a utility tower in accordance withthe present invention, where the transmitters have been replaced withelectronic cards having the same functionality. The interface to theelectronic card is now “virtual”, through the HMI. The utility towerstill contains signal translators and aggregators.

FIG. 9a shows a physical transmitter (9.1), the display parameters(9.2), and the keypad functions (9.3) in accordance with the prior art.

FIG. 9b shows a calibration display screen (9.5).

FIGS. 9c and d shows a menu tree for a dissolved oxygen transmitter inaccordance with the prior art.

FIG. 9e shows a “virtual” transmitter in accordance with the presentinvention which mimics the display and keypad functions of the physicaltransmitter shown in FIGS. 9a and 9b . This “virtual” transmitter willshow the same or functionally equivalent display screens and have thesame menu tree as the physical transmitter, but is implemented in thesoftware of the HMI.

FIG. 10a shows a connection of traditional sensor output signals to theelectronics card inside the utility tower in accordance with the presentinvention.

FIG. 10b shows the connection of either traditional or new sensorsthrough “readers” that replace the electronic card in the utility tower.The outputs of the sensors are now either standard analog signals (withno diagnostics) or digital bus signals (with full diagnostics). Thesesensors are “hot-pluggable” to the utility tower.

FIG. 11 is a schematic in accordance with the present invention whichshows the layout of a utility tower where the electronic cardfunctionality is implemented outside of the utility tower and insideeither a sensor reader or the sensor probe itself. The interface to thesensor is “virtual”, through the HMI. The utility tower still containssignal translators and aggregators.

FIG. 12 shows a bioreactor control system in accordance with the presentinvention that is fully digital. The sensors, pump tower, and gasmanifold all connect to the utility tower using cables that carrydigital bus communications. The utility tower is connected to thecontroller using the same digital bus protocol. In this design, thetransmitter functionality is contained within the sensor (i.e., isdistributed), and the utility tower provides an aggregator for all ofthe digital signals.

DESCRIPTION OF THE INVENTION

As described above, a central or distributed prior art processing systemlike that shown in

FIG. 1, which controls one or a plurality of bioreactors, is typicallyaccompanied by an HMI. An intuitive yet capable HMI is important, sothat attempts to simplify and optimize this interface have been made.The HMI interface is most often an interactive display on a computermonitor or a touch screen that is utilized to show the informationrequired by a user to maintain control of the bio-process. FIG. 6 showsan example of a typical prior art bioprocess HMI for an autoclavable,glass vessel. The information displayed usually includes a graphicalrepresentation of the bioreactor 6.1, detailed control parameter valuesand any associated process set-points 6.2, primary system hardwarecomponents 6.3 (e.g. pumps, mass flow controller, scales), and alsoalarms and warnings 6.4.

The HMI software usually has several different pages. FIG. 7 shows atypical “overview” page, where the user can see basic information aboutthe configuration of each process vessel. FIG. 7a shows a typicalconfiguration page of the HMI, where the bio-process engineer can setprocess parameters 7.1 and program control strategies and loops 7.2. Inmany automation systems, once the process strategy is set, the user canstore all of the configuration and startup information in a file, forlater upload, or propagation to other vessels. Many of these automationfunctions and display graphics have become commonplace in mostautomation HMI interfaces, so that a new user can learn to set up theirprocess quickly.

However, in prior art automation systems, the sensor transmitters arenot readily physically accessible, therefore when using the HMI, the enduser needs to learn how to use proprietary and unfamiliar interfaces. Inthe most extreme situation, either the transmitter electronics are soproprietary that the user must access the boards to change settings orcalibrate the transmitter (e.g., with dip-switches or potentiometers),or the user has no access to the transmitter at all. In automationsystems employing digital transmitters, the HMI(shown in FIG. 7b ) cancontain a graphical 7.3, or tabular 7.4, “faceplate” which providesinformation about the sensor and transmitter data stream and settings.In some automation systems, the digital transmitter can be calibrated orits measurement standardized and the settings stored so that the userhas a record of the sensor parameters that can be viewed in acalibration “window” 7.5. Such graphical HMI systems, although morecapable than the menu-driven, generally less expensive automationsystems, usually do not provide full access to all transmitterfunctions. They are also not as intuitive or easy for the user to learn,understand and use.

As manufacturers strive to reduce the cost of bioprocess controlhardware while simultaneously maximizing the information obtained from agiven bioreactor, it is desirable to eliminate any redundant componentsin the system design. In many cases, a significant fraction of a utilitytower's component cost is represented by the digital transmitters. Wehave found that by using electronic cards (the printed circuit boardspresent inside the transmitter) having equivalent functionality tomeasure and transmit primary, secondary, and even tertiary processvariables, as well as to receive calibration commands and/or performdiagnostic sequences, it is possible to replace the conventional digitaltransmitters and eliminate the significant cost of the transmitterpackaging (e.g., enclosure, display, keypad, etc.). This allows for useof “non-dedicated” components, or more specifically components thatserve multiple purposes as opposed to being dedicated to one specificfunction. For example, the keyboard associated with the HMI (a userinput and information display device) can be used to input thetemperature, pH, dissolved oxygen, dissolved CO₂, or any relevantanalyte's information, as opposed to using a separate dedicated keyboardassociated with each transmitter for each of the aforementioned sensors.The digital controller used in the bioprocess automation system of thepresent invention can replace the dedicated microprocessor used in eachindividual transmitter. In addition, if electronics boards are designedto communicate with a digital bus, then the need for a translator blockis eliminated, leading to further simplification and cost savings.

The bioreactor monitoring and control system of the present inventionutilizes only non-dedicated user input and information display devices,a digital controller and software, and therefore comprises:

i) one or more diagnostic sensor probes for measuring an operatingcondition in the bioreactor

ii) means, such as an electric or fiber optic cable, for transmittingthe diagnostic signal from the probe (or each of the probes) to

iii) signal conditioning and communication electronics (a card or cards)which supply operating current and/or voltage to said probe and whichconvert the diagnostic signal into a format accessible by

iv) a controller which directly receives the format converted signalfrom the card and transmits it to

v) a monitor which includes software which enables the monitor todisplay the converted signal and also, when appropriate, to instruct thecontroller to implement changes in the operating conditions in thebioreactor

vi) a software-based virtual transmitter which substantially replicatesthe keyboard, display, menu-tree and response of a physical sensortransmitter.

The software based virtual transmitter of the present inventiontherefore does not need a separate physical keyboard to enter data butit performs the function and action of a physical transmitter, and hasequivalent measurement capability. Specifically referring to FIG. 5, thekeyboards 5.3 shown on the physical transmitters are no longernecessary. Additionally, the entire case 5.1 holding the keyboard andthe display 5.2 for this transmitter are entirely unnecessary as thisfunctionality can be addressed by the bioreactor control systems HMI.Looking at FIG. 3a ((3.1) a keyboard and monitor is clearly shown wherethe display of FIG. 9e would appear, including the virtual transmitterrepresentation.

FIG. 8 shows how such electronic signal conditioning cards for pH 8.1 ordissolved oxygen (DO) 8.2, having the same functional capacity as atraditional transmitter, can be directly plugged into the utility (ortransmitter) tower digital bus. Note that the cards still receive thesensor input via cables 8.3 and are directly connected 8.4 into the mainsignal aggregator 8.5. The translator has been eliminated from theutility tower, while the other analog/digital inputs 8.6 from otherhardware such has pumps, scales, and agitator motors and theirassociated translator/aggregator 8.7 remain unchanged, and continue toprovide additional input 8.8 into the main signal aggregator 8.5. Themain signal aggregator's output 8.9 remains connected to the controller,as in FIG. 4. Thus, the utility tower architecture of the reduced costsystem of the present invention shown in FIG. 8 is similar to theoriginal utility tower architecture shown in FIG. 4, but the translatorhas been deleted, and the third party transmitters have been replacedwith electronic cards that perform the same function, but which requireno packaging or display. In this configuration, the HMI (e.g., a mouseor touch-screen) can be directly used to set-up the electronic cardconfiguration, and also to calibrate/configure each sensor, as if usinga physical transmitter.

By using transmitter cards in the utility tower that have equivalentfunctionality to a transmitter such as is commonly used in the industry,it is possible to create a user interface for the HMI that effectivelymimics the physical transmitter 9.1 shown in FIG. 9a . The concept of a“virtual” transmitter in accordance with the present invention is thatthe look and feel associated with the prior art, physical transmitter ismimicked by the HMI software and graphics. The functions of theoriginal, physical transmitter are accessible through the HMI, withoutthe need to open the utility tower to see a physical display 9.2 orpunch commands into a physical keypad 9.3, and without the cost of thetransmitter 9.1. The command sequences 9.5 in FIG. 9b are an example oftemperature calibration of a DO sensor. The menu-tree in FIGS. 9c and 9dis an example of a menu tree from a DO transmitter such as one made byRosemount Analytical, and all associated features of a traditionaltransmitter can be implemented “virtually” within the HMI software ofthe automation system. FIG. 9e illustrates how such a “virtual”transmitter, in accordance with the present invention, can beimplemented within the HMI from FIG. 7 to mimic a physical DOtransmitter such as the one made by Rosemount Analytical. By clicking onthe Dissolved Oxygen window 9.7,(where is 9.7?) the user would activatethe “virtual” transmitter graphic 9.8. The simulated displays screens9.9 allows the user to read the data stream and display prompts from the“virtual” transmitter, while the simulated keyboard graphic 9.10 allowsthe user to enter data or commands into the “virtual” transmitter.

Thus, the “virtual” transmitter concept of the present invention allowsthe user to seamlessly transition from prior art physical transmitterswith familiar commands, calibration procedures, and menu trees to thenovel control system of the present invention which provides improvedcapability and self-monitoring, without having to learn a newtransmitter interface, and without any ambiguity imposed by the HMI'sinterpretation of the transmitter operation. Moreover, because the“virtual” transmitter is implemented as a pure gateway for the transferof sensor data into the control system, and since it does not itselfstore any of the data, it is not governed by 21 CFR part 11requirements, and will therefore not affect the overall automationsystem's 21 CFR part 11 compliance.

Minimizing the validation required for a new technology is always a keyfactor in its adoption by the biopharmaceutical industry. A system mustbe able to be validated if it is to be used in research or processdevelopment, and then scaled into GMP applications. For the virtualtransmitter, both the electronic cards and the software must be tested,and demonstrate substantially equivalent performance to the transmittersthey are replacing.

Specifically, the electronic cards used in the present invention provideperformance and functionality substantially identical to those of theoriginal transmitter, and this interchangeability can be readilydemonstrated and documented with straightforward performance testing.Similarly, by mimicking the physical transmitter in the HMI as describedpreviously and validating the software implementation for each “virtual”transmitter the automation system manufacturer can test and then provideessentially identical performance. The end result is that not only willthe end user experience a seamless transition from the physical to the“virtual” transmitter, but any existing standard operating procedures(SOP) used by the end user in quality and validation documentation willremain unchanged. The requirement that a “virtual” transmitter mimic atraditional, physical transmitter enables an upgrade to existingautomation system having traditional sensors and measurement methods.However, for new measurement methods or novel sensor designs, thevirtual transmitter concept of the present invention can be implementedwith greater capability and flexibility.

In the embodiment of the present invention described previously, andillustrated generally in FIGS. 8 and 9 c, and in further detail in FIG.10a , a traditional transmitter is replaced by an electronic signalconditioning card 10.1 inside the utility tower of a bioreactor controlsystem, and the HMI user interface is programmed to display a “virtual”transmitter image that mimics the display and command set of a physicaltransmitter. In this architecture, the sensor 10.3 still has nointelligence, but only transmits its raw output signals to itscorresponding electronic card 10.1, e.g., using electrical cables 10.2.Similarly, disposable sensors having a “transducer” 10.4 that containsthe optical/electrical elements necessary to measure the raw signal froma disposable element 10.5 inserted inside the process vessel, transmitsthe raw sensor output to a corresponding electronic card 10.1 using anelectrical cable 10.2. Note that this concept can even be extended tofiber-optic based disposable or autoclavable sensors whose optics andelectronics are housed on the electronic card 10.1 inside the utilitytower, and where cable 10.2 is not an electrical cable but rather anoptical fiber, and the sensor 10.3 is a physical adapter by which theend of the fiber is inserted inside the bioprocess vessel or is incontact with the active element (e.g., a fluorescent material). Thisconcept can also be extended to systems where the fluid in thebioreactor itself is the active element (e.g.: when detection involvesRaman scattering or NIR spectroscopy).

In the prior art configurations, if the type of sensor is changed or ifadditional redundancy is needed for a specific measurement, then theutility tower must be opened and the physical electronic cardconfiguration must be modified accordingly. Such physical changes to thehardware either require the electronic cards to be “hot-pluggable” bythe end user, or alternatively require the end user to call a fieldservice or in-house automation engineer/technician to make the hardwarechange. In all cases, the automation system must be powered down, sothat changes can only be made in between growth runs, and usually needto be scheduled. Furthermore, a re-calibration of all sensors must beexecuted after the hardware change, to ensure that the physical cardsand sensors work together correctly, resulting in additional time andlabor costs. In GMP applications, if the hardware is modified, thecorresponding changes must be set in the input/output modules of theautomation system, and the new system re-validated and re-tested, whichleads to yet additional labor and schedule delays.

In order to resolve these limitations, and make the sensors“hot-swappable” or configurable “on-the-fly”, the electronic cardfunctionality must be moved outside of the utility tower and closer tothe sensor, as shown in FIG. 10b . For traditional sensors 10.6, theelectronic card can be miniaturized and packaged inside “reader” 10.7that locks onto the sensor's connector. The output of “reader” 10.7 is adigital bus protocol, such as Modbus, Foundation Fieldbus, DeviceNet, orProfiBus, so that the reader is connected with the utility tower 10.9 bymeans of a standard bus interface cable 10.10. For new types of sensors,such as optical or disposable sensors 10.8, the “transducer” andtransmitter electronics can suitably be integrated into the “reader”10.7. The output of “reader” 10.7 for the new sensor would also be adigital bus protocol. Note that cables 10.10 would all be identical (fora same bus protocol) and be independent of the sensor type, whereascables 10.2 depend on the connector type of the sensor, and would varyfrom sensor to sensor.

The sensor signals on cables 10.2 in FIG. 10a are most frequentlyanalog, whereas the signals on sensor cables 10.10 in FIG. 10b aredigital, so that their transmission is more robust and immune to noiseingress. Furthermore, cables 10.10 carry information about the sensorreading as well as sensor identification, diagnostics, and calibrationdata. Note that with further miniaturization, the “reader” electronicscan be integrated directly into the sensor body, so that the sensor 10.6can be connected directly to cable 10.10.

In the design configuration of FIG. 10b , the sensors are hot-swappable,so that new or redundant sensors can be added to the utility tower atany time, because the automation system can extract the necessaryinformation from the sensor “reader”. If communications standards areset for the bus interface and “reader” commands, such a system could betested and validated by the manufacturer for a group of pre-approvedsensors, both internally designed or from third party manufacturers. Theend user can then change the sensor configuration automatically, andwithout the need to re-validate the hardware and software automationsystems.

FIG. 11 demonstrates how the digital “readers” can provide inputs 11.1directly into the main signal aggregator 11.2 inside the utility tower.This design allows for the control system to rapidly identify andcommunicate with each sensor and obtain a full set of sensor calibrationdata and diagnostics. The other signals from the analog and digitalaggregator/translator 11.4 reach the main signal aggregator 11.2 byconnector 11.5, and would be merged with the sensor digital signals 11.1prior to output 11.6 to the controller and automation system.

Note that if diagnostics and calibration are not required, a simpler andless expensive version of the sensor “reader” can be implemented. Inthis embodiment, the “reader” would measure the raw sensor readings andtransmit them either as a standard analog (4 to 20 mA) or digital (0 to10 V) signal, without the full bus communications protocol. In thiscase, cables 10.10 would suitably be standard two-wire cables, ratherthan digital bus cables, and the sensor output 11.3 could enter theanalog and digital aggregator/translator 11.4 inside the utility tower.

In yet another embodiment of the present invention, the electronics ofan optical sensor, such a fluorescence-based pH or dissolved oxygensensor, can mimic the sensor output of a traditional electrochemical orpolarographic sensor, respectively, and provide their output to the same“reader” 10.7 employed by traditional electrochemical probes. Forexample, the electronics inside the sensor could transform the opticalsignal into a voltage output (mV) for the optical pH sensor, and into acurrent output (40 to 80 nA) for the dissolved oxygen sensor. By usingthe same connector (e.g., VP-style) on the optical sensor, it coulddirectly replace the traditional sensor in this architecture.

In the above scenario, it is also possible to use the electronics in theprobe to allow the user to perform the calibration at the probe, andthen use the cards in the bioprocess automation system to simply and/orfurther condition the signals. For instance with a dissolved oxygenprobe, the user would follow the typical calibration path of putting theprobe in two different known environments (e.g.: 0% oxygen and 100%water saturated air) and have the values recorded by the probe. Theelectronics and software in the probe would then be used to create thedetailed connection between the two values, so that the probe isconsistent and accurate.

FIG. 12 shows a schematic of a system in accordance with the presentinvention having digital sensors with readers directly integrated intothe sensor shaft (or body). In this design, the transmitterfunctionality is contained within each sensor, and the utility towersimply provides an aggregator for all of the digital signals. Utilitytower 12.1 can be connected to “hot-pluggable” sensors 12.1 withelectrical cables 12.3, much in the same way as it would be connected toa pump tower 12.4 using cable 12.5 or a gas manifold 12.6 using cable12.7. The utility tower can then be connected using cable 12.9 to thecontroller cabinet 12.8. The controller cabinet can be connected to thesupervisory PC as well as additional HMI workstations. Note that thissystem can be designed so that cables 12.3, 12.5, and 12.7 are alldigital bus cables, and the sensors and actuator towers (pump tower 12.4and gas manifold 12.6) all employ the same digital bus protocol. Thefunctionality of the utility tower would then be reduced to providingsignal aggregation to the controller.

In this approach, the functionality of the original transmitters insidethe utility tower has been transferred to the sensors themselves. Thecost of the transmitter function is significantly reduced because thetransmitter enclosure, display, and keypad are eliminated. Furthermore,if all of the sensors employ the same digital protocol and same menutree, then the cost of programming and validating of each transmitter isreduced, so that the engineering and quality check-out (validation)costs of developing the utility tower are lower, and allow for morecompetitive pricing of the final product.

1-4. (canceled)
 5. A bioreactor monitoring and control systemcomprising: i) at least one in situ diagnostic probe for measuringoperating conditions in a bioreactor; ii) an electronic card comprisingsignal conditioning and communication electronics for supplyingoperating voltage and/or current to the at least one in situ diagnosticprobe, and converting a diagnostic signal from the at least one in situdiagnostic sensor probe into a format-converted signal; iii) a digitalprocessor comprising a non-transitory computer-readable medium, thenon-transitory computer-readable medium comprising instructions forreceiving the format-converted signal and transmits transmitting it toiv) a display device to present: a) a human machine interface, and b) asoftware based virtual transmitter which replicates the keyboard,display, menu-tree and response of a physical transmitter, wherein thesoftware based virtual transmitter is configured to be displayed on thehuman machine interface, wherein the software based virtual transmitteris configured to show the format-converted signal, and wherein theelectronic card interfaces with the software based virtual transmitterto enable the software based virtual transmitter to perform the functionand action of a physical transmitter.
 6. A process for monitoring andcontrolling a bioprocess being carried out in a bioreactor, said processcomprising: i) providing said bioreactor with at least one in situdiagnostic probe for measuring operating conditions in said bioreactor;ii) using signal conditioning and communication electronics to supplyoperating current and/or voltage to said at least one in situ diagnosticprobe and convert a diagnostic signal from said at least one in situdiagnostic probe into a format-converted signal accessible by a digitalcontroller; iii) transmitting the format-converted signal to the digitalcontroller; and iv) transmitting the format-converted signal from thedigital controller to a display device for: presenting theformat-converted signal in a software-based virtual transmitter whichsubstantially replicates the keyboard, display, menu-tree and responseof a physical sensor transmitter.
 7. The process of claim 6, furthercomprising integrating the signal conditioning and communicationelectronics with said at least one diagnostic probe.
 8. The process ofclaim 6 further comprising integrating the signal conditioningelectronics with means for transmitting the diagnostic signal in anelectronic card.
 9. The process of claim 8, wherein the electronic cardboth sends diagnostic signals to and receives diagnostic signals fromthe at least one diagnostic probe.
 10. The process of claim 8, furthercomprising transmitting the diagnostic signal from the at least onediagnostic probe to the electronic card via a fiber optic cable.
 11. Theprocess of claim 8, wherein the electronic card is capable of performingfunctions of the physical sensor transmitter.
 12. The process of claim8, further comprising disposing the electronic card outside a utilitytower and configuring the at least one in situ diagnostic probe to behot swappable into the utility tower.
 13. The process of claim 8,further comprising disposing the electronic card within a utility tower.14. The process of claim 13, further comprising transmitting theformat-converted signal to the utility tower.
 15. The process of claim13, wherein the electronic card is configured to transmit theformat-converted signals from each of the at least one in situdiagnostic probe to the utility tower.
 16. The process of claim 13,wherein the utility tower contains signal aggregators.
 17. The processof claim 13, wherein the utility tower is connected to the digitalcontroller using a digital bus protocol.
 18. The process of claim 6,wherein the virtual transmitter is configured not to store data from theformat-converted signal.
 19. The process of claim 6, further comprisingaccessing the software-based virtual transmitter using a non-dedicatedhuman machine interface.
 20. The process of claim 19, further comprisingaccessing functions of a physical transmitter using the software basedvirtual transmitter via the non-dedicated human machine interface. 21.The process of claim 6, further comprising changing at least oneoperating condition in the bioreactor in response to receiving theformat-converted signal from the digital controller.
 22. The process ofclaim 6, further comprising measuring at least one of the followingbioreactor process parameters: pH, dissolved oxygen, temperature ordissolved carbon dioxide using the software-based virtual transmitter.23. The process of claim 6, wherein the signal conditioning andcommunication electronics includes means for transmitting theformat-converted signal.
 24. The process of claim 6, wherein the virtualtransmitter includes means for transmitting process variables andreceiving calibration commands.